Abstract
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a single-stranded RNA coronavirus that causes nervous dysfunction in the infected hosts and leads to widespread alterations in the host transcriptome by modulating specific microRNA (miRNA) levels. MiRNAs contribute to RNA virus pathogenesis by promoting antiviral immune response, enhancing viral replication, or altering miRNA-mediated host gene regulation. Thus, exploration of the virus–miRNA interactions occurring in PHEV-infected host may lead to the identification of novel mechanisms combating the virus life cycle or pathogenesis. Here, we discovered that the expression of miR-10a-5p was constitutively up-regulated by PHEV in both the N2a cells in vitro and mice brain in vivo. Treatment with miR-10a-5p mimics allowed miR-10a-5p enrichment and resulted in a significant restriction in PHEV replication, suggesting widespread negative regulation of the RNA virus infection by miR-10a-5p. The outcomes were also evidenced by miR-10a-5p inhibitor over-expression. Luciferase reporter, quantitative real-time PCR (qRT-PCR), and western blotting analysis further showed that Syndecan 1 (SDC1), a cell surface proteoglycan associated with host defense mechanisms, acts as a target gene of miR-10a-5p during PHEV infection. Naturally, siRNA-mediated knockdown of SDC1 leads to a reduction in viral replication, implying that SDC1 expression is likely a favorable condition for viral replication. Together, the findings demonstrated that the abundant miR-10a-5p leads to downstream suppression of SDC1, and it functions as an antiviral mechanism in the PHEV-induced disease, providing a potential strategy for the prevention and treatment of PHEV infection in the future work.
Highlights
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a neurotropic coronavirus and causes central nervous system (CNS) disorders and digestive illnesses in piglets (Li et al, 2016)
A miRNA array was previously performed to identify the miRNAs involved in neurological dysfunction as a result of PHEV infection (Figure 1A and Supplementary Data Sheet S1)
Of these upregulated miRNAs, we found that miR-10a-5p was of research value and practical significance
Summary
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a neurotropic coronavirus and causes central nervous system (CNS) disorders and digestive illnesses in piglets (Li et al, 2016). The main host of PHEV infection is the piglets under 3 weeks of age, manifested by vomiting and wasting disease (VWD) or encephalomyelitis, with a mortality rate of nearly 100% (Vijgen et al, 2006). Increasing studies demonstrate that miRNAs are involved in host–virus interactions and actively regulate the replication of pathogenic viruses (Haasnoot and Berkhout, 2011). Host cells utilized miR-26a to defend against porcine reproductive and respiratory syndrome virus (PRRSV) infection by activating innate antiviral immunity (Jia et al, 2015). Several viruses hijack host miRNAs to promote their replication, such as miR-146a, which promotes HBV replication by targeting zinc finger e-box binding homeobox 2 (ZEB2) (Wang and Li, 2018). Our previous research found that some miRNAs, such as miR-21a and miR-142-5p, are involved in PHEV infection (Li et al, 2017; Lv et al, 2017), and these findings lead to a better understanding of miRNA-mediated regulation of PHEV infection
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